Gender medicine ‘built on shaky foundations’, Cass review finds

Researchers studied 23 guidelines published in different countries between 1998 and 2022, finding most lacked an evidence-based approach. Photograph: Ronnie Chua/Getty Images/iStockphoto

The head of the world’s largest review into children’s care has said that gender medicine is “built on shaky foundations”.

Dr Hilary Cass, the paediatrician commissioned to conduct a review of the services provided by the NHS to children and young people questioning their gender identity, said that while doctors tended to be cautious in implementing new findings in emerging areas of medicine, “quite the reverse happened in the field of gender care for children”.

Cass commissioned the University of York to conduct a series of analyses as part of her review.

Two papers examined the quality and development of current guidelines and recommendations for managing gender dysphoria in children and young people. Most of the 23 clinical guidelines reviewed were not independent or evidence based, the researchers found.

A third paper on puberty blockers found that of 50 studies, only one was of high quality.

Similarly, of 53 studies included in a fourth paper on the use of hormone treatment, only one was of sufficiently high quality, with little or only inconsistent evidence on key outcomes.

Here are the main findings of the reviews:

Clinical guidelines

Increasing numbers of children and young people experiencing gender dysphoria are being referred to specialist gender services. There are various guidelines outlining approaches to the clinical care of these children and adolescents.

In the first two papers, the York researchers examined the quality and development of published guidelines or clinical guidance containing recommendations for managing gender dysphoria in children and young people up to the age of 18.

They studied a total of 23 guidelines published in different countries between 1998 and 2022. All but two were published after 2010.

Most of them lacked “an independent and evidence-based approach and information about how recommendations were developed”, the researchers said.

Few guidelines were informed by a systematic review of empirical evidence and they lack transparency about how their recommendations were developed. Only two reported consulting directly with children and young people during their development, the York academics found.

“Healthcare services and professionals should take into account the poor quality and interrelated nature of published guidance to support the management of children and adolescents experiencing gender dysphoria/incongruence,” the researchers wrote.

Writing in the British Medical Journal (BMJ), Cass said that while medicine was usually based on the pillars of integrating the best available research evidence with clinical expertise, and patient values and preferences, she “found that in gender medicine those pillars are built on shaky foundations”.

She said the World Professional Association of Transgender Healthcare (WPATH) had been “highly influential in directing international practice, although its guidelines were found by the University of York’s appraisal to lack developmental rigour and transparency”.

In the foreword to her report, Cass said while doctors tended to be cautious in implementing new findings “quite the reverse happened in the field of gender care for children”.

In one example, she said a single Dutch medical study, “suggesting puberty blockers may improve psychological wellbeing for a narrowly defined group of children with gender incongruence”, had formed the basis for their use to “spread at pace to other countries”. Subsequently, there was a “greater readiness to start masculinising/feminising hormones in mid-teens”.

She added: “Some practitioners abandoned normal clinical approaches to holistic assessment, which has meant that this group of young people have been exceptionalised compared to other young people with similarly complex presentations. They deserve very much better.”

Both papers repeatedly pointed to a key problem in this area of medicine: a dearth of good data.

She said: “Filling this knowledge gap would be of great help to the young people wanting to make informed choices about their treatment.”

Cass said the NHS should put in place a “full programme of research” looking at the characteristics, interventions and outcomes of every young person presenting to gender services, with consent routinely sought for enrolment in a research study that followed them into adulthood.

Gender medicine was “an area of remarkably weak evidence”, her review found, with study results also “exaggerated or misrepresented by people on all sides of the debate to support their viewpoint”.

Alongside a puberty blocker trial, which could be in place by December, there should be research into psychosocial interventions and the use of the masculinising and feminising hormones testosterone and oestrogen, the review found.

Hormone treatment

Many trans people who seek medical intervention in their transition opt to take hormones to masculinise or feminise their body, an approach that has been used in transgender adults for decades.

“It is a well-established practice that has transformed the lives of many transgender people,” the Cass review notes, adding that while these drugs are not without long-term problems and side-effects, for many they are dramatically outweighed by the benefits.

For birth-registered females, the approach means taking testosterone, which brings about changes including the growth of facial hair and a deepening of the voice, while for birth-registered males, it involves taking hormones including oestrogen to promote changes including the growth of breasts and an increase in body fat. Some of these changes may be irreversible.

However, in recent years a growing proportion of adolescents have begun taking these cross-sex, or gender-affirming, hormones, with the vast majority who are prescribed puberty blockers subsequently moving on to such medication.

This growing take-up among young people has led to questions over the impact of these hormones in areas ranging from mental health to sexual functioning and fertility.

Now researchers at the University of York have carried out a review of the evidence, comprising an analysis of 53 previously published studies, in an attempt to set out what is known – and what is not – about the risks, benefits and possible side-effects of such hormones on young people.

All but one study, which looked at side-effects, were rated of moderate or low quality, with the researchers finding limited evidence for the impact of such hormones on trans adolescents with respect to outcomes, including gender dysphoria and body satisfaction.

The researchers noted inconsistent findings around the impact of such hormones on growth, height, bone health and cardiometabolic effects, such as BMI and cholesterol markers. In addition, they found no study assessed fertility in birth-registered females, and only one looked at fertility in birth-registered males.

“These findings add to other systematic reviews in concluding there is insufficient and/or inconsistent evidence about the risks and benefits of hormone interventions in this population,” the authors write.

However, the review did find some evidence that masculinising or feminising hormones might help with psychological health in young trans people. An analysis of five studies in the area suggested hormone treatment may improve depression, anxiety and other aspects of mental health in adolescents after 12 months of treatment, with three of four studies reporting an improvement around suicidality and/or self-harm (one reported no change).

But unpicking the precise role of such hormones is difficult. “Most studies included adolescents who received puberty suppression, making it difficult to determine the effects of hormones alone,” the authors write, adding that robust research on psychological health with long-term follow-up was needed.

The Cass review has recommended NHS England should review the current policy on masculinising or feminising hormones, advising that while there should be the option to provide such drugs from age 16, extreme caution was recommended, and there should be a clear clinical rationale for not waiting until an individual reached 18.

Puberty blockers

Treatments to suppress puberty in adolescents became available through routine clinical practice in the UK a decade ago.

While the drugs have long been used to treat precocious puberty – when children start puberty at an extremely young age – they have only been used off-label in children with gender dysphoria or incongruence since the late 1990s. The rationale for giving puberty blockers, which originated in the Netherlands, was to buy thinking time for young people and improve their ability to smooth their transition in later life.

Data from gender clinics reported in the Cass review showed the vast majority of people who started puberty suppression went on to have masculinising or feminising hormones, suggesting that puberty blockers did not buy people time to think.

To understand the broader effects of puberty blockers, researchers at the University of York identified 50 papers that reported on the effects of the drugs in adolescents with gender dysphoria or incongruence. According to their systematic review, only one of these studies was high quality, with a further 25 papers regarded as moderate quality. The remaining 24 were deemed too weak to be included in the analysis.

Many of the reports looked at how well puberty was suppressed and the treatment’s side-effects, but fewer looked at whether the drugs had their intended benefits.

Of two studies that investigated gender dysphoria and body satisfaction, neither found a change after receiving puberty blockers. The York team found “very limited” evidence that puberty blockers improved mental health.

Overall, the researchers said “no conclusions” could be drawn about the impact on gender dysphoria, mental and psychosocial health or cognitive development, though there was some evidence bone health and height may be compromised during treatment.

Based on the York work, the Cass review finds that puberty blockers offer no obvious benefit in helping transgender males to help their transition in later life, particularly if the drugs do not lead to an increase in height in adult life. For transgender females, the benefits of stopping irreversible changes such as a deeper voice and facial hair have to be weighed up against the need for penile growth should the person opt for vaginoplasty, the creation of a vagina and vulva.

In March, NHS England announced that children with gender dysphoria would no longer receive puberty blockers as routine practice. Instead, their use will be confined to a trial that the Cass review says should form part of a broader research programme into the effects of masculinising and feminising hormones.